Immune function decreases with age as evidenced by the age-correlated increase in susceptibility to infections, neoplastic diseases, and autoimmune diseases. The causes of the senescence of the immune system aren't understood but it is associated with and, probably, in large part, due to the involution of the thymus gland and the decrease in the concentration of thymic hormones in the blood which begins after sexual maturation and progresses through old age. It has been observed that growth hormone secretion by the pituitary also decreases with advancing age and that growth hormone has a thymotrophic effect. These observations lead to the hypothesis that perhaps decreasing production of growth hormone by the adenohypophysis plays a role in the progressive decrease in thymus size and the secretion of thymus hormones with age. The objective of the proposed research is to further characterize the influence of growth hormone on the thymus gland and immune system of the aging dog. The specific aims are to: 1) determine in normal dogs the serum concentration of the thymus hormones thymosin alpha 1 and thymosin beta 4 from birth through old age; 2) determine serum thymosin alpha 1 and thymosin beta 4 concentration in middle-aged dogs before, during and after growth hormone administration; and 3) evaluate the ultrastructure of thymic epithelial cells in young dogs and in middle-aged dogs before and after growth hormone treatment. If growth hormone administration to aging dogs will stimulate the thymus to increase its production of thymus hormones, it may have an impact on the incidence or severity of diseases associated with senescence of the immune system. The information gained in the proposed experimentation would provide the basis for further experimentation on growth hormone administration to aging dogs with spontaneously occurring autoimmune or neoplastic conditions.